The overall objective of this research program is to probe further into the biochemical perturbations of disease involving the last stages of human blood coagulation, that is, the formation of fibrin and its interactions with other proteins. It is the long-term goal of this research to define the interactions of fibrinogen-fibrin with factor XIII and fibronectin both in healthy and in disease stages. The specific aims of this project include the isolation and characterization of the specific biochemical defects associated with three congenitally abnormal human fibrinogen variants and the isolation and characterization of the factor XIIIa crosslinking site in plasma fibronectin. The specific goals for the coming year include preliminary studies on the specific interactive properties of intact plasma fibronectin and fibrinogen-fibrin during the assembly process and specific studies to characterize the abnormality in fibrinogen Chapel Hill II.